tbuckley/cabot-search huggingface dataset:
Thou shall not heal: Overcoming the non-healing behaviour of diabetic foot ulcers by engineering the inflammatory microenvironment
Authors: Michael G. Monaghan, Rajiv Borah, Charlotte Thomsen, Shane Browne
Journal: Advanced Drug Delivery Reviews (2023)

Diabetic foot ulcers (DFUs) are a devastating complication for diabetic patients that have debilitating effects and can ultimately lead to limb amputation. Healthy wounds progress through the phases of healing leading to tissue regeneration and restoration of the barrier function of the skin. In contrast, in diabetic patients dysregulation of these phases leads to chronic, non-healing wounds. In particular, unresolved inflammation in the DFU microenvironment has been identified as a key facet of chronic wounds in hyperglyceamic patients, as DFUs fail to progress beyond the inflammatory phase and towards resolution. Thus, control over and modulation of the inflammatory response is a promising therapeutic avenue for DFU treatment. This review discusses the current state-of-the art regarding control of the inflammatory response in the DFU microenvironment, with a specific focus on the development of biomaterials-based delivery strategies and their cargos to direct tissue regeneration in the DFU microenvironment.
Emerging insights into atypical B cells in pediatric chronic infectious diseases and immune system disorders: T(o)-bet on control of B-cell immune activation
Authors: Giulio Olivieri, Nicola Cotugno, Paolo Palma
Journal: Journal of Allergy and Clinical Immunology (2023)

Repetitive or persistent cellular stimulation in vivo has been associated with the development of a heterogeneous B-cell population that exhibits a distinctive phenotype and, in addition to classical B-cell markers, often expresses the transcription factor T-bet and myeloid marker CD11c. Research suggests that this atypical population consists of B cells with distinct B-cell receptor specificities capable of binding the antigens responsible for their development. The expansion of this population occurs in the presence of chronic inflammatory conditions and autoimmune diseases where different nomenclatures have been used to describe them. However, as a result of the diverse contexts in which they have been investigated, these cells have remained largely enigmatic, with much ambiguity remaining regarding their phenotype and function in humoral immune response as well as their role in autoimmunity. Atypical B cells have garnered considerable interest because of their ability to produce specific antibodies and/or autoantibodies and because of their association with key disease manifestations. Although they have been widely described in the context of adults, little information is present for children. Therefore, the aim of this narrative review is to describe the characteristics of this population, suggest their function in pediatric immune-related diseases and chronic infections, and explore their potential therapeutic avenues.
SIRT5 rs12216101 T&gt;G variant is associated with liver damage and mitochondrial dysfunction in patients with non-alcoholic fatty liver disease
Authors: Federico Salomone, Rosaria Maria Pipitone, Miriam Longo, Francesco Malvestiti, Angela Maria Amorini, Alfio Distefano, Elia Casirati, Ester Ciociola, Nunzio Iraci, Loredana Leggio, Rossella Zito, Nunzio Vicario, Concetta Saoca, Grazia Pennisi, Daniela Cabibi, Giuseppe Lazzarino, Anna Ludovica Fracanzani, Paola Dongiovanni, Luca Valenti, Salvatore Petta, Giovanni Li Volti, Stefania Grimaudo
Journal: Journal of Hepatology (2023)
Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas
Authors: Enrique Blanco-Carmona, Ashwin Narayanan, Inmaculada Hernandez, Juan C. Nieto, Marc Elosua-Bayes, Xueyuan Sun, Claudia Schmidt, Necmettin Pamir, Koray Özduman, Christel Herold-Mende, Francesca Pagani, Manuela Cominelli, Julian Taranda, Wolfgang Wick, Andreas von Deimling, Pietro Luigi Poliani, Michael Rehli, Matthias Schlesner, Holger Heyn, Şevin Turcan
Journal: Cell Reports Medicine (2023)

The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA and ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition to astrocyte-like, oligodendrocyte progenitor-like, and cycling tumor subpopulations, a tumor population enriched for ribosomal genes and translation elongation factors is primarily present in oligodendrogliomas. Longitudinal analysis of astrocytomas indicates that the proportion of tumor subpopulations remains stable in recurrent tumors. Analysis of tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, with astrocytomas harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions between tumor subpopulations and TAMs may contribute to TAM state diversity. Overall, our study sheds light on distinct tumor populations, TAM heterogeneity, TAM-tumor interactions in IDH-mutant glioma subtypes, and the relative stability of tumor subpopulations in recurrent astrocytomas.
Disseminated mucormycosis in a child with acute lymphoblastic leukemia (case report)
Authors: E. S. Shchelkanova, G. V. Tereshchenko, Alexey S. Krasnov
Journal: Radiology - Practice (2023)

Mucormycosis is a rare invasive fungal infection most commonly seen in patients with oncological and hematological diseases, when receiving chemotherapy treatment especially in the neutropenic phase. Early diagnosis and timely initiation of treatment are extremely important to improve the prognosis and survival of the patient. In this article, we present a clinical case of a very rare variant of disseminated mucormycosis with involvement of the spleen and mediastinum in a 21-month-old child due to Lichtheimia spp.
Minimally Invasive Treatment of Abdominal Abscesses in Children Using Ultrasound Navigation
Authors: A. A. Yusufov, G. N. Rumyantseva, A. Yu. Gorshkov, A. N. Kazakov, D. G. Galakhova, V. N. Kartashev
Journal: Radiology - Practice (2023)

The article provides a brief review of the literature on the diagnosis and management tactics of children with abdominal abscesses. A study of the literature has shown that open methods of treating abdominal abscesses are still the most common in children’s practice, although puncturedrainage techniques have obvious advantages. This publication presents an analysis of the results of five years of experience in the treatment of children with abdominal abscesses using minimally invasive technologies. A unique clinical case of multiple abdominal abscesses in a 10-year-old child undergoing outpatient treatment for gastroduodenitis without an effect is described in detail. During hospitalization, an ultrasound examination (ultrasound) was performed, multiple abscesses of the abdominal cavity of various localization and sizes were found. The method of percutaneous minimally invasive surgical intervention under ultrasound control was chosen as the treatment tactic. The above observation shows the wide possibilities of ultrasound in the diagnosis and treatment of abdominal abscesses in children.
Ultrasound Diagnostic of Testicular ischemia without torsion in children. Rare clinical observations
Authors: M. V. Topolnik
Journal: Radiology - Practice (2023)

Testicular ischemia is the most serious complication of acute pathology of the scrotum, the etiopathogenesis of which is quite diverse and still remains an urgent issue for discussion. The most well-known cause of testicular ischemia is testicular torsion. All other variants are found casually rarely (orchoepididymitis, incarcerated inguinal-scrotal hernia, thrombosis of the veins of the pampiniform plexus, etc.). This paper presents clinical observations of acute testicular ischemia of various etiologies, illustrated with echographic scans and intraoperative images. The publication is supplemented with a brief review of the literature.
Non-Invasive Technique for MRI Diagnostics of Bone Marrow Cellularity in Children with Acute Lymphoblastic Leukemia
Authors: G. V. Tereshchenko, N. A. Kriventsova, D. A. Kupriyanov, D. V. Litvinov, G. A. Novichkova
Journal: Radiology - Practice (2023)

Evaluation of the apparent fat fraction (FF) changes in patients at different stages of leukemia treatment compared with children without hematological disorders. The study included 24 healthy volunteers (control group), 40 patients with leukemia: 20 in the acute phase of the disease and 20 patients after chemotherapy in hematopoietic aplasia. Four regions of interest were chosen in size of 150 mm 2 : in the body of the right and left iliac bones, as well as in the bodies of L4 and L5 vertebras. FF significantly changes in patients with leukemia regarding the control group. Quantitative MRI images is a new method for assessing changes in the bone marrow of children with leukemia.
Ultrasound Diagnostic of Torsion of Omental Lymphangioma in a Child with Intestinal Intussusception
Authors: E. B. Olkhova, M. V. Topolnik, I. S. Allakhverdiev
Journal: Radiology - Practice (2023)

Torsion of omental lymphangioma is a extremely rarity, the echographic picture is nonspecific (thin–walled cystic formation) and the diagnosis in the vast majority of cases is made only intraoperatively. It is almost never possible to reliably visualize actually torsion in the form of a whirlpool-sign. The article presents our own observation of the torsion of lymphangioma of the greater omentum in a 2-year-old girl. The onset of the disease was associated with the occurrence of intestinal intussusception, during the diagnosis of which, as a «random finding», a cystic formation of the abdominal cavity was revealed. The child underwent repeated ultrasound and CT scans, which made it possible to reliably visualize the torsion of the cystic formation. The final diagnosis was made intraoperatively. The clinical observation is illustrated by ultrasound and radiologic scans and intraoperative images. The publication is supplemented with a brief review of the literature.
Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism
Authors: Miguel Cosenza-Contreras, Agnes Schäfer, Justin Sing, Lena Cook, Maren N Stillger, Chia-Yi Chen, Jose Villacorta Hidalgo, Niko Pinter, Larissa Meyer, Tilman Werner, Darleen Bug, Zeno Haberl, Oliver Kübeck, Kai Zhao, Susanne Stei, Anca Violeta Gafencu, Radu Ionita, Felix M Brehar, Jaime Ferrer-Lozano, Gloria Ribas, Leo Cerdá-Alberich, Luis Martí-Bonmatí, Christopher Nimsky, Alexis Van Straaten, Martin L Biniossek, Melanie Föll, Nina Cabezas-Wallscheid, Jörg Büscher, Hannes Röst, Armelle Arnoux, Jörg W Bartsch, Oliver Schilling
Journal: Neuro-Oncology (2023)

There is an urgent need to better understand the mechanisms associated with the development, progression, and onset of recurrence after initial surgery in glioblastoma (GBM). The use of integrative phenotype-focused -omics technologies such as proteomics and lipidomics provides an unbiased approach to explore the molecular evolution of the tumor and its associated environment.
Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function
Authors: Maria Borrell-Pages, Aureli Luquero, Gemma Vilahur, Teresa Padró, Lina Badimon
Journal: Cardiovascular Research (2023)

Abstract Aims There is little information on the regulation of cholesterol homeostasis in the brain. Whether cholesterol crosses the blood–brain barrier is under investigation, but the present understanding is that cholesterol metabolism in the brain is independent from that in peripheral tissues. Lipoprotein receptors from the LDL receptor family (LRPs) have key roles in lipid particle accumulation in cells involved in vascular and cardiac pathophysiology; however, their function on neural cells is unknown. Methods and results The expression of LRP5 and the components and targets of its downstream signalling pathway, the canonical Wnt pathway, including β-catenin, LEF1, VEGF, OPN, MMP7, and ADAM10, is analysed in the brains of Wt and Lrp5−/− mice and in a neuroblastoma cell line. LRP5 expression is increased in a time- and dose-dependent manner after lipid loading in neuronal cells; however, it does not participate in cholesterol homeostasis as shown by intracellular lipid accumulation analyses. Neurons challenged with staurosporin and H2O2 display an anti-apoptotic protective role for LRP5. Conclusions For the first time, it has been shown that neurons can accumulate intracellular lipids and lipid uptake is performed mainly by the LDLR, while CD36, LRP1, and LRP5 do not play a major role. In addition, it has been shown that LRP5 triggers the canonical Wnt pathway in neuronal cells to generate pro-survival signals. Finally, Lrp5−/− mice have maintained expression of LRP5 only in the brain supporting the biological plausible concept of the need of brain LRP5 to elicit pro-survival processes and embryonic viability.
Extramedullary Hematopoiesis in Treated Diffuse Large B-Cell Lymphoma of Bone
Authors: Amine Chaouki, Véronique Roelants, Olivier Gheysens, Sarah Bailly, Bruno Krug
Journal: Clinical Nuclear Medicine (2023)

A 65-year-old man with a history of diffuse large B-cell bone lymphoma of the right radius underwent an interim FDG PET/CT after 2 cycles of chemotherapy. Besides a complete metabolic response on the primary site, images revealed a hypermetabolic nodule in the posterior mediastinum, not present on the initial images. The metabolic activity of the nodule was similar to that of the reactive bone marrow and disappeared, concomitantly to the normalization of the medullar signal on the posttreatment images. The similarity and synchronous metabolic activity evolution in the nodule and bone marrow indicate extramedullary hematopoiesis.
Increasing proportions of extended-spectrum β-lactamase-producing isolates among Escherichia coli from urine and bloodstream infections: results from a nationwide surveillance network, Finland, 2008 to 2019
Authors: Heikki Ilmavirta, Jukka Ollgren, Kati Räisänen, Tuure Kinnunen, Antti J Hakanen, Jari Jalava, Outi Lyytikäinen
Journal: Eurosurveillance (2023)

Background Escherichia coli is the leading cause of urinary tract infections (UTI) and bloodstream infections (BSI), and the emergence of antimicrobial resistance (AMR) in E. coli causes concern. Aim To investigate changes in the proportion of extended-spectrum β-lactamase (ESBL) producing isolates among E. coli isolated from urine and blood in Finland during 2008–2019. Methods Susceptibility testing of 1,568,488 urine (90% female, 10% male) and 47,927 blood E. coli isolates (61% female, 39% male) from all Finnish clinical microbiology laboratories during 2008–2019 was performed according to guidelines from the Clinical and Laboratory Standard Institute during 2008–2010 and the European Committee on Antimicrobial Susceptibility Testing during 2011–2019. A binomial regression model with log link compared observed trends over time and by age group and sex. Results The annual proportion of ESBL-producing E. coli isolates among E. coli from blood cultures increased from 2.4% (23/966) to 8.6% (190/2,197) among males (average annual increase 7.7%; 95% CI: 4.4–11.0%, p &lt; 0.01) and from 1.6% (28/1,806) to 6.4% (207/3,218) among females (9.3%; 95% CI: 4.8–14.0%, p &lt; 0.01). In urine cultures, the proportion of ESBL-producing E. coli isolates increased from 2.2% (239/10,806) to 7.2% (1,098/15,297) among males (8.8%; 95% CI: 6.5–11.3%, p &lt; 0.01) and from 1.0% (1,045/108,390) to 3.1% (3,717/120,671) among females (8.6%; 95% CI: 6.3–11.0%, p &lt; 0.01). A significant increase was observed within most age groups. Conclusions Considering the ageing population and their risk of E. coli BSI and UTI, the increase in the annual proportions of ESBL-producing E. coli is concerning, and these increasing trends should be carefully monitored.
State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies
Authors: Whitney S. Thompson, Samir N. Babayev, Michelle L. McGowan, Andrea G. Kattah, Myra J. Wick, Ellen M. Bendel-Stenzel, Fouad T. Chebib, Peter C. Harris, Neera K. Dahl, Vicente E. Torres, Christian Hanna
Journal: Journal of the American Society of Nephrology (2023)

There is a broad phenotypic spectrum of monogenic polycystic kidney diseases (PKDs). These disorders often involve cilia-related genes and lead to the development of fluid-filled cysts and eventual kidney function decline and failure. Preimplantation genetic testing for monogenic (PGT-M) disorders has moved into the clinical realm. It allows prospective parents to avoid passing on heritable diseases to their children, including monogenic PKD. The PGT-M process involves embryo generation through in vitro fertilization, with subsequent testing of embryos and selective transfer of those that do not harbor the specific disease-causing variant(s). There is a growing body of literature supporting the success of PGT-M for autosomal-dominant and autosomal-recessive PKD, although with important technical limitations in some cases. This technology can be applied to many other types of monogenic PKD and ciliopathies despite the lack of existing reports in the literature. PGT-M for monogenic PKD, like other forms of assisted reproductive technology, raises important ethical questions. When considering PGT-M for kidney diseases, as well as the potential to avoid disease in future generations, there are regulatory and ethical considerations. These include limited government regulation and unstandardized consent processes, potential technical errors, high cost and equity concerns, risks associated with pregnancy for mothers with kidney disease, and the impact on all involved in the process, including the children who were made possible with this technology.
DGKα/ζ inhibitors combine with PD-1 checkpoint therapy to promote T cell–mediated antitumor immunity
Authors: Michael Wichroski, Joseph Benci, Si-Qi Liu, Louis Chupak, Jie Fang, Carolyn Cao, Cindy Wang, Joelle Onorato, Hongchen Qiu, Yongli Shan, Dana Banas, Ryan Powles, Gregory Locke, Abigail Witt, Caitlyn Stromko, Huilin Qi, Xiaofan Zheng, Scott Martin, Min Ding, Robert Gentles, Nicholas Meanwell, Upender Velaparthi, Richard Olson, Susan Wee, Daniel Tenney, Christopher G. Parker, Benjamin F. Cravatt, Michael Lawrence, Robert Borzilleri, Emma Lees
Journal: Science Translational Medicine (2023)

Programmed cell death protein 1 (PD-1) immune checkpoint blockade therapy has revolutionized cancer treatment. Although PD-1 blockade is effective in a subset of patients with cancer, many fail to respond because of either primary or acquired resistance. Thus, next-generation strategies are needed to expand the depth and breadth of clinical responses. Toward this end, we designed a human primary T cell phenotypic high-throughput screening strategy to identify small molecules with distinct and complementary mechanisms of action to PD-1 checkpoint blockade. Through these efforts, we selected and optimized a chemical series that showed robust potentiation of T cell activation and combinatorial activity with αPD-1 blockade. Target identification was facilitated by chemical proteomic profiling with a lipid-based photoaffinity probe, which displayed enhanced binding to diacylglycerol kinase α (DGKα) in the presence of the active compound, a phenomenon that correlated with the translocation of DGKα to the plasma membrane. We further found that optimized leads within this chemical series were potent and selective inhibitors of both DGKα and DGKζ, lipid kinases that constitute an intracellular T cell checkpoint that blunts T cell signaling through diacylglycerol metabolism. We show that dual DGKα/ζ inhibition amplified suboptimal T cell receptor signaling mediated by low-affinity antigen presentation and low major histocompatibility complex class I expression on tumor cells, both hallmarks of resistance to PD-1 blockade. In addition, DGKα/ζ inhibitors combined with αPD-1 therapy to elicit robust tumor regression in syngeneic mouse tumor models. Together, these findings support targeting DGKα/ζ as a next-generation T cell immune checkpoint strategy.
Expanding Treatment Options for Older Adults With Prostate Cancer
Authors: Alicia Morgans
Journal: JAMA Oncology (2023)

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Cardiac noradrenergic deficiency revealed by 18F-dopamine positron emission tomography identifies preclinical central Lewy body diseases
Authors: David S Goldstein, Courtney Holmes, Patti Sullivan, Grisel Lopez, Janna Gelsomino, Sarah Moore, Risa Isonaka, Tianxia Wu, Yehonatan Sharabi
Journal: Journal of Clinical Investigation (2023)

In Lewy body diseases (LBDs) Parkinson disease (PD), and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction manifests clinically, substantial neurodegeneration has already occurred. Biomarkers are needed to identify central LBDs in a preclinical phase, when neurorescue strategies might forestall symptomatic disease. This phase may involve catecholamine deficiency in the autonomic nervous system. We analyzed data from the prospective, observational, long-term PDRisk study to assess the predictive value of low versus normal cardiac 18F-dopamine positron emission tomography (PET), an index of myocardial content of the sympathetic neurotransmitter norepinephrine, in at-risk individuals.
Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: JAMA Internal Medicine (2023)